The effect of sex on antipyrine metabolism in cattle at different ages

The aim of this study was to determine the effect of sex on the metabolism of antipyrine by measuring the antipyrine plasma clearance as well as excretion of three major metabolites in urine in cattle of different ages. The experiment was carried out on 10 female and 10 male cattle of Black and White breed. The antipyrine test was carried out at 1, 2, 4, 6, 8, 12 and 18 months of age for each animal (single dose of 10 mg/kg antipyrine were given intravenously). The concentrations of antipyrine, 4-hydroxyantipyrine (4-OHA), 3-hydroxymethylantipyrine (HMA) and norantipyrine (NORA) were measured in plasma and urine by high performance liquid chromatography (HPLC). The apparent volume of distribution of antipyrine (aVd) decreased significantly between 1 and 18 months of age, but mean aVd values observed in males and females were not statistically different. The experimental period was characterised by a steady decrease (statistically significant) in antipyrine half-life (t1/2beta). These values did not differ significantly between males and females under 12 months. In 12 and 18 month-old animals the antipyrine half-life in the females was significantly shorter than in the males. The systemic clearance (Cls) of antipyrine increased significantly between 1 and 18 months of age. No significant differences were observed between systemic clearance of antipyrine in males and females under 12 months. In 12 and 18 month-old animals the Cls values were significantly higher in females than in males. Following intravenous administration, recovery of antipyrine and its three main metabolites increased significantly with age. These values did not differ significantly between males and females under 12 month of age. In 12 and 18 month-old females the excretion of 4-OHA and HMA in urine was significantly higher than in males at the same age. The excretion of NORA and unchanged antipyrine in males and females did not differ significantly. The partial clearances of antipyrine metabolites (Cl(m)) increased significantly between 1 and 18 months of age. No significant differences were observed between Cl(m) values in males and females under 12 months of age. In 12 and 18 month-old females the partial clearances of 4-OHA and HMA were significantly higher than in males. The clearance of NORA was significantly higher in 18 month-old females than in males. In conclusion, we report a sex-linked difference in plasma antipyrine clearance and urinary excretion of the main metabolites of antipyrine in cattle over 12 months of age, the females being the more active metabolizers.